Preparation and Evaluation in Vivo and in Vitro of Tulobuterol Crystal Reservoir Patch / 中国药学杂志

ABSTRACT

OBJECTIVE: To prepare the tulobuterol crystal reservoir patch, and to evaluate morphology, stability and crystallization factors of the crystal in the patch, adhesive force, dissolution, transdermal properties in vitro and the pharmacokinetics in rabbits. METHODS: The transdermal patch was prepared on the basis of drug recrystallization and characterized by morphology, stability and crystallization factors using microscope and adhesive force using initial adhesion tester, adhesion tester and peel tester. The dissolution and transdermal properties were evaluated by using the dissolution tester and transdermal tester. In addition, pharmacokinetics was studied using New Zealand rabbits as experimental animals. RESULTS: The drug crystals were evenly distributed in the form of filaments, which had average width of (4.4±1.8)μm and kept stable at 2-40 ℃. The crystallization in patches is affected by tulobuterol supersaturation and temperature. The adhesive force of patch was suitable and its dissolution matched standard which can be fitted by the Higuchi equation. In the diffusion cell in vitro, the drug penetrated through the skin in a Zero-order kinetic equation, and the cumulative penetration percentage and skin retention concentration were 92.04% and 10.36 μg·cm-2 with in 24 h. The pharmaceutic parameters showed that the tulobuterol blood concentration can be maintained within 24 h, whose tmax and ρmax were (6.67±3.06)h and (3.08±1.32) ng·mL-1, respectively. CONCLUSION: The tulobuterol crystal reservoir patch can be established by control of recrystallization conditions. The patch has good adhesive properties and sustained release characteristics in vitro and in vivo, which has the practical significance for further study.